The World Gastroenterology Organization published a set of guidelines listing symptoms related to inflammatory damage of the digestive tract that may be indicative of IBD, including:1
Diarrhea: stool may contain mucus or blood, may manifest as nocturnal diarrhea or incontinence
Constipation: this may be the primary symptom in UC limited to the rectum; obstipation that can be seen in cases of bowel obstruction
Bowel movement abnormalities manifesting as pain, rectal bleeding, bowel movement urgency, and tenesmus
Abdominal cramping and pain: commonly present in the right lower quadrant of the abdomen in CD or around the umbilicus and in the left lower quadrant of the abdomen in moderate to severe UC
Nausea and vomiting which is more common in CD than in UC
Despite increased understanding of potential risk factors that may affect the development and progression of IBD, no research has been able to identify the exact causes of the disease. As a result, there is a lack of specific and adequate diagnostic tests and procedures.
IBD is a systemic inflammatory disease and can affect organs other than the gastrointestinal tract. Up to 47% of patients with IBD have at least one extra-intestinal manifestation, which may include dermatological (e.g., pyoderma gangrenosum, erythema nodosum), ocular (e.g., uveitis, conjunctivitis), rheumatological (e.g., spondyloarthropathy, arthralgia) or hepatic disorders (e.g., primary sclerosing cholangitis).2These clinical symptoms are not specifically defined and require a broad differential diagnosis. Before computerized tomography (CT) was part of routine examination, CD was frequently diagnosed at the time of laparotomy for presumed appendicitis. To establish the correct diagnosis, symptoms must be evaluated holistically, including endoscopic and radiological findings.Endoscopic evaluation is considered the current standard of IBD diagnosis, but it has significant limitations including cost, complexity, invasiveness, and risk of complications – for example, a risk of perforation of the intestines is evaluated as 4.5-9.7 cases per 10,000 patients.3
In terms of treatment options, there is a high demand for non-invasive biomarkers that have the potential to avoid invasive diagnostic tests and possible complication. There are a number of biomarkers currently used in clinical practice, but there is no single one which can help with an accurate diagnosis of IBD. Relevant biomarkers can be divided into two groups based on their application:
Group 1: diagnosis and monitoring of IBD
Group 2: subclassification of IBD to UC and CD
The first group, aimed at diagnosis and monitoring of IBD, contains blood-based biomarkers of inflammation (C-reactive protein and erythrocyte sedimentation rate) and stool-based biomarkers (e.g., fecal calprotectin, fecal lactoferrin, fecal neopterin, and polymorphonuclear neutrophil elastase). The second group of biomarkers, aimed at the subclassification of IBD between UC and CD, includes blood-based biomarkers antineutrophil cytoplasmic antibodies (ANCAs), anti–outer membrane protein C (Anti-OmpC), anti–S. cerevisiae antibodies (ASCA), anti-I2 antibody, anti-carbohydrate antibodies, and pancreatic antibodies.4
There is no universally accepted biomarker for an ultimate diagnosis of IBD, and these biomarkers can only be used as supporting data secondary to clinical data and endoscopic examination. Another limitation of biomarkers is their inability to predict response to therapy in patients with IBD. Inflammatory biomarkers are non-specific and can appear normal during the disease flare, so they do not provide a diagnostic or predictive value in IBD setting.
With the frequent primary lack of response (or loss of response as typically seen with biologics therapy), predictive biomarkers are more vital than ever. They can serve to both “catch” the disease at the earliest possible moment for starting the treatment and to understand when the therapy stops working, thus helping reduce exposure to ineffective treatment and eliminate adverse events.